Acute Inescapable Stress Rapidly Increases Synaptic Energy Metabolism in Prefrontal Cortex and Alters Working Memory Performance

Abstract

Brain energy metabolism actively regulates synaptic transmission and activity. We have previously shown that acute footshock (FS)-stress induces fast and long-lasting functional and morphological changes at excitatory synapses in prefrontal cortex (PFC). Here, we asked whether FS-stress increased energy metabolism in PFC, and modified related cognitive functions. Using positron emission tomography (PET), we found that FS-stress induced a redistribution of glucose metabolism in the brain, with relative decrease of [18F]FDG uptake in ventro-caudal regions and increase in dorso-rostral ones. Absolute [18F]FDG uptake was inversely correlated with serum corticosterone. Increased specific hexokinase activity was also measured in purified PFC synaptosomes (but not in total extract) of FS-stressed rats, which positively correlated with 2-Deoxy [3H] glucose uptake by synaptosomes. In line with increased synaptic energy demand, using an electron microscopy-based stereological approach, we found that acute stress induced a redistribution of mitochondria at excitatory synapses, together with an increase in their volume. The fast functional and metabolic activation of PFC induced by acute stress, was accompanied by rapid and sustained alterations of working memory performance in delayed response to T-maze test. Taken together, the present data suggest that acute stress increases energy consumption at PFC synaptic terminals and alters working memory.

Mitochondrial gene signature in the prefrontal cortex for differential susceptibility to chronic stress

“…Given that glucose is the main source of energy for the mammalian brain 64 , through a key contribution to OXPHOS processes 65 , the observed increases in genes coding for OXPHOS complexes subunits may be an allostatic response to compensate for reduced fuel 28 , 66 , 67 . However, given that our neurobiological endpoints were only measured after chronic stress exposure, we cannot discard that they are not a reaction to stress-induced enhancements in mitochondrial function potentially observed at earlier time points 56 , 68 , particularly in the PFC 69 . Eventually, the reported compensatory changes could represent responses to the “allostatic load” induced by chronic stress 70 .…”

Acute Ketamine Facilitates Fear Memory Extinction in a Rat Model of PTSD Along With Restoring Glutamatergic Alterations and Dendritic Atrophy in the Prefrontal Cortex

“…Animals were subjected to a single session of acute inescapable FS stress as previously reported ( Musazzi et al, 2019 ): intermittent shocks (0.8 mA) for 40 min (20 min total of actual shock with random intershock length between 2 and 8 s). The FS box was connected to a scrambler controller (LE 100-26, Panlab) that delivers intermittent shocks to the metallic floor.…”

The Acute Stress Response in the Multiomic Era

“…Surprisingly little is known about changes in mitochondria in response to acute stress. In the medial prefrontal cortex (mPFC), acute stress leads to a surge in neuronal activity, triggering an increase in glucose metabolism and synaptic uptake of glucose and increasing the number and size of mitochondria (54). In contrast, metabolic analysis after chronic stress showed reduced mitochondrial respiration and glucose availability in the mPFC (55).…”